Human pluripotent stem cell‐derived lung organoids: Potential applications in development and disease modeling. (3rd November 2020) - Tian, Lu
Abstract: The pulmonary system is comprised of two main compartments, airways and alveolar space. Their tissue and cellular complexity ensure lung function and protection from external agents, for example, virus. Two‐dimensional (2D) in vitro systems and animal models have been largely employed to elucidate the molecular mechanisms underlying human lung development, physiology, and pathogenesis. However, neither of these models accurately recapitulate the human lung environment and cellular crosstalk. More recently, human‐derived three‐dimensional (3D) models have been generated allowing for a deeper understanding of cell‐to‐cell communication. However, the availability and accessibility of primary human cell sources from which generate the 2D and 3D models may be limited. In the past few years, protocols have been developed to successfully employ human pluripotent stem cells (hPSCs) and differentiate them toward pulmonary fate in vitro . In the present review, we discuss the advantages and pitfalls of hPSC‐derived lung 2D and 3D models, including the main characteristics and potentials for these models and their current and future applications for modeling development and diseases. Lung organoids currently represent the closest model to the human pulmonary system. We further focus on the applications of lung organoids for the study of human diseases such as pulmonary fibrosis, infectious diseases, and lung cancer. Finally, we discuss the present limitations and potential future applications of 3D lung organoids. This article is categorized under: Adult Stem Cells, Tissue Renewal, and Regeneration > Stem Cells and Disease Adult Stem Cells, Tissue Renewal, and Regeneration > Stem Cell Differentiation and Reversion Abstract : The advent of human pluripotent stem cells (hPSCs) presents unprecedented opportunities to study human development and model diseases. Differentiated cells derived from hPSCs in two‐dimensional (2D) and three‐dimensional (3D) cultures have proven to be a reliable model for studying lung development, exploring lung disease pathogenesis and underlying mechanisms. Here we provide an overview of recent progress in hPSC‐derived lung 2D and 3D models, discussing their advantages and limitations in modeling lung diseases and their potential use to develop new drugs.